Dosing & Uses
Dosage Forms & Strengths
oral solution
- 200mg/mL (450mL/bottle)
Rett Syndrome
Indicated for treatment of Rett syndrome
35 kg to <50 kg: 10,000 mg (50 mL) PO BID
≥50 kg: 12,000 mg (60 mL) PO BID
Dosage Modifications
Diarrhea or weight loss
- Advise patients to stop laxatives before initiating
- Interrupt, reduce dosage, or discontinue if severe diarrhea occurs, if dehydration suspected, or if significant weight loss occurs
Renal impairment
- No dedicated study has been conducted to evaluate pharmacokinetics in patients with renal impairment
- Moderate-to-severe: Not recommended; eliminated mainly through the kidney
Hepatic impairment
- No dose adjustment required; not significantly metabolized by liver
Dosing Considerations
Discontinue laxatives before initiating
Monitor weight during treatment
Dosage Forms & Strengths
oral solution
- 200mg/mL (450mL/bottle)
Rett Syndrome
Indicated for treatment of Rett syndromein adults and children aged ≥2 years
9 kg to <12 kg: 5,000 mg (25 mL) PO BID
12 kg to <20 kg: 6,000 mg (30 mL) PO BID
20 kg to <35 kg: 8,000 (40 mL) PO BID
35 kg to <50 kg: 10,000 mg (50 mL) PO BID
≥50 kg: 12,000 mg (60 mL) PO BID
Dosage Modifications
Diarrhea or weight loss
- Advise patients to stop laxatives before initiating
- Interrupt, reduce dosage, or discontinue if severe diarrhea occurs, if dehydration suspected, or if significant weight loss occurs
Renal impairment
- No dedicated study has been conducted to evaluate pharmacokinetics in patients with renal impairment
- Moderate-to-severe: Not recommended; eliminated mainly through the kidney
Hepatic impairment
- No dose adjustment required; not significantly metabolized by liver
Dosing Considerations
Discontinue laxatives before initiating
Monitor weight during treatment
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (41)
- ambrisentan
trofinetide will increase the level or effect of ambrisentan by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- atogepant
trofinetide will increase the level or effect of atogepant by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- atorvastatin
trofinetide will increase the level or effect of atorvastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- bosentan
trofinetide will increase the level or effect of bosentan by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- caspofungin
trofinetide will increase the level or effect of caspofungin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- digoxin
trofinetide will increase the level or effect of digoxin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- elagolix
trofinetide will increase the level or effect of elagolix by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- elbasvir/grazoprevir
trofinetide will increase the level or effect of elbasvir/grazoprevir by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- eluxadoline
trofinetide will increase the level or effect of eluxadoline by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- enalapril
trofinetide will increase the level or effect of enalapril by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- erythromycin base
trofinetide will increase the level or effect of erythromycin base by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- erythromycin ethylsuccinate
trofinetide will increase the level or effect of erythromycin ethylsuccinate by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- erythromycin lactobionate
trofinetide will increase the level or effect of erythromycin lactobionate by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- erythromycin stearate
trofinetide will increase the level or effect of erythromycin stearate by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- ezetimibe
trofinetide will increase the level or effect of ezetimibe by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- fexofenadine
trofinetide will increase the level or effect of fexofenadine by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- fluvastatin
trofinetide will increase the level or effect of fluvastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- glecaprevir/pibrentasvir
trofinetide will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- glyburide
trofinetide will increase the level or effect of glyburide by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- imatinib
trofinetide will increase the level or effect of imatinib by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- letermovir
trofinetide will increase the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- levothyroxine
trofinetide will increase the level or effect of levothyroxine by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- lovastatin
trofinetide will increase the level or effect of lovastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- methotrexate
trofinetide will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- olmesartan
trofinetide will increase the level or effect of olmesartan by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- paclitaxel
trofinetide will increase the level or effect of paclitaxel by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- penicillin G benzathine
trofinetide will increase the level or effect of penicillin G benzathine by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- pitavastatin
trofinetide will increase the level or effect of pitavastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- pravastatin
trofinetide will increase the level or effect of pravastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- repaglinide
trofinetide will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- revefenacin
trofinetide will increase the level or effect of revefenacin by Other (see comment). Avoid or Use Alternate Drug. rofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- rifampin
trofinetide will increase the level or effect of rifampin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- rosuvastatin
trofinetide will increase the level or effect of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- sacubitril/valsartan
trofinetide will increase the level or effect of sacubitril/valsartan by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- simvastatin
trofinetide will increase the level or effect of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- sulbactam/durlobactam
trofinetide will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations
- telmisartan
trofinetide will increase the level or effect of telmisartan by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- troglitazone
trofinetide will increase the level or effect of troglitazone by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- valsartan
trofinetide will increase the level or effect of valsartan by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- voxilaprevir
trofinetide will increase the level or effect of voxilaprevir by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
- zavegepant intranasal
trofinetide will increase the level or effect of zavegepant intranasal by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
Monitor Closely (30)
- alfentanil
trofinetide will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- carbamazepine
trofinetide will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- clonidine
trofinetide will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- colchicine
trofinetide will increase the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- cyclosporine
trofinetide will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- dihydroergotamine
trofinetide will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- disopyramide
trofinetide will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- divalproex sodium
trofinetide will increase the level or effect of divalproex sodium by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- ergotamine
trofinetide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- ethosuximide
trofinetide will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- everolimus
trofinetide will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- fentanyl
trofinetide will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- fosphenytoin
trofinetide will increase the level or effect of fosphenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- midazolam
trofinetide will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- momelotinib
trofinetide increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- pacritinib
trofinetide will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- phenobarbital
trofinetide will increase the level or effect of phenobarbital by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- phenytoin
trofinetide will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- pimozide
trofinetide will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- primidone
trofinetide will increase the level or effect of primidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- quinidine
trofinetide will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- quinine
trofinetide will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- repaglinide
trofinetide will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- sirolimus
trofinetide will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- tacrolimus
trofinetide will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- theophylline
trofinetide will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- thioridazine
trofinetide will increase the level or effect of thioridazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- triazolam
trofinetide will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- valproic acid
trofinetide will increase the level or effect of valproic acid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
- warfarin
trofinetide will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
Minor (0)
Adverse Effects
>10%
Diarrhea (82%)
Diarrhea, persistent or recurrent after dose interruptions, reductions, or concomitant antidiarrheal therapy (49%)
Vomiting (29%)
1-10%
Fever (9%)
Seizure (9%)
Anxiety (8%)
Decreased appetite (8%)
Fatigue (8%)
Nasopharyngitis (5%)
Warnings
Contraindications
None
Cautions
Diarrhea
- Diarrhea expected in most patients and ranges in severity
- Advise patients to stop laxatives before starting
- If diarrhea occurs, have patient notify healthcare provider
- Consider starting antidiarrheal treatment, and monitor hydration status and increase oral fluids, if needed
- Interrupt, reduce dose, or discontinue if severe diarrhea occurs or if dehydration suspected
Weight loss
- Weight loss may occur
- Monitor weight and interrupt, reduce dose, or discontinue if significant weight loss occurs
Drug interaction overview
Inhibitor of CYP3A4 (weak), OATP1B1, and OATP1B3
-
Sensitive CYP3A4 substrates
- Closely monitor
- Coadministration may increase plasma concentrations of orally administered CYP3A4 sensitive substrates
- Monitor CYP3A4 substrates for which a small change in substrate plasma concentration may lead to serious toxicities
-
Sensitive OATP1B1 or OATP13 substrates
- Avoid coadministration
- Trofinetide inhibits OATP1B1 and OATP1B3 in vitro
- Avoid with substrates for which a small change in substrate plasma concentration may lead to serious toxicities
Pregnancy & Lactation
Pregnancy
There are no adequate data on developmental risks associated with use in pregnant females
Animal studies
- No adverse developmental effects observed following administration to pregnant animals at doses associated with plasma exposures below those used clinically
Lactation
Data are not available regarding presence of trofinetide or its metabolites in human milk, effects on breastfed infants, or effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown
Synthetic analog of the amino‐terminal tripeptide of insulinlike growth factor (IGF-1) designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function, specifically, the protein fragment glypromate (GPE)
GPE consist of the amino acids glycine-proline-glutamate; trofinetide is a modified form of GPE allowing it to be stable and administered orally, unlike GPE or IGF-1
IGF-1 is produced by both major types of brain cells – neurons and glia; IGF-1 in the brain is critical for both normal development and response to injury and disease
Trofinetide has been shown to inhibit the production of inflammatory cytokines, inhibit overactivation of microglia and astrocytes, and increase amount of available IGF-1 that can bind to IGF-1 receptors
Absorption
Peak plasma time: 2-3 hr
Bioavailability: ≥84%
Effect of food: High-fat meal had not impact on AUC and reduce peak plasma concentration ~20%
Distribution
Protein bound: <6%
Vd: ~80 L
Metabolism
Not significantly metabolized by CYP450 enzymes
Hepatic metabolism is not a significant route of elimination
Elimination
Half-life: 1.5 hr
Excretion: Urine ~80% (unchanged); feces (minor)
Administration
Oral Administration
May take with or without food
Administer orally or via gastrostomy (G) tube; doses administered via gastrojejunal (GJ) tubes must be administered through the G-port
Use calibrated measuring device (eg, oral syringe or oral dosing cup) to measure and deliver prescribed dose accurately; household measuring cup is not an adequate measuring device
Missed or vomited dose
- If dose missed, take next dose as scheduled; do not double dose
- If dose vomited, do not take an additional dose; instead, continue with next scheduled dose
Storage
- Refrigerate bottle in upright position at 2-8ºC (36-46ºF)
- Do not freeze
- Keep child-resistant cap tightly closed
- Discard any unused oral solution after 14 days of first opening bottle
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Formulary
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